Long-term inhalation toxicity of N-vinylpyrrolidone-2 vapours. Studies in rats.
In previous subchronic studies inhaled N-vinylpyrrolidone-2 (NVP) was haemotoxic, hepatotoxic and irritant to the nose. In the first of two long-term studies, study A, Sprague-Dawley rats were exposed by inhalation to 0, 5, 10 or 20 ppm NVP (6 hr/day, 5 days/wk) for 24 months. Satellite groups were killed after 3, 12 or 24 months. In study B, female Sprague-Dawley rats were exposed to 0 or 45 ppm NVP for 3 months and killed at 3 or 12 and 24 months post-exposure. In study A, survival was unaffected, but reduced body weight gain, haemotoxicity, effects on clinical chemistry parameters indicative of hepatotoxicity, increased liver weight, hepatocellular carcinomas, necrosis, reparative hyperplasia, adenomas and adenocarcinomas of the nasal cavity, and squamous cell carcinomas of the larynx were seen. Increased tumour incidence was seen only in the liver and upper respiratory tract. In study B, the effect of NVP on body weight evident at 3 months disappeared before 1 yr, but effects on liver pathology persisted throughout the subsequent 21-month exposure-free period, and a few liver tumours were seen at 2 yr. As NVP gave negative results in a battery of in vitro and in vivo genotoxicity tests, it appears that the tumours that arose were manifestations of a non-genotoxic mechanism.
Klimisch
H J
HJ
BASF Aktiengesellschaft, Department of Toxicology, Ludwigshafen, Germany.
Deckardt
K
K
Gembardt
C
C
Hildebrand
B
B
Küttler
K
K
Roe
F J
FJ
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity*; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D004435:Eating / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009296:Nasal Cavity / Q000187:drug effects; D009369:Neoplasms / Q000139:chemically induced*; D009669:Nose Neoplasms / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011760:Pyrrolidinones / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000187:drug effects / Q000378:metabolism
D001672:Biocompatible Materials; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; D005723:gamma-Glutamyltransferase; D005978:Glutathione